Chlamydiae are intracellular bacterial pathogens that are responsible for a wide variety of important human and animal infections.
Chlamydia trachomatis is transmitted between human beings through social or sexual contact. A number of Chlamydia trachomatis serovars exist, and although the identification and classification of serovars continues to evolve, at least 18 have been reported to date. Serovars A to C are primarily associated with ocular trachoma, serovars D to K with oculogenital disease and serovars L1 to L3 with lymphogranuloma venereum (LGV) (Brunham, R C et al. J. Nat. Rev. Immunol. 2005 5:149-161).
Chlamydia trachomatis is one of the most common causes of sexually transmitted diseases and can lead to pelvic inflammatory disease (PID), resulting in tubal obstruction and infertility. Chlamydia trachomatis may also play a role in male infertility. In 1990, the cost of treating PID in the US was estimated to be $4 billion. The World Health Organisation estimated that in 1999 over 90 million new cases of sexually transmitted Chlamydia trachomatis occurred worldwide (Global Prevalence and Incidence of Selected Curable Sexually Transmitted Infections, World Health Organisation, Geneva, 2001). Furthermore, ulcerative sexually transmitted diseases such as Chlamydia trachomatis infection are a major risk factor for HIV acquisition (Brunham, R C et al. J. Nat. Rev. Immunol. 2005 5:149-161; Igietseme, J U et al. Expert Rev. Vaccines 2003 2(1):129-146).
Trachoma, due to ocular infection with Chlamydia trachomatis, is the leading cause of preventable blindness worldwide and is estimated to affect 300-500 million people (West, S K Prog. Ret. Eye Res. 2004 23:381-401). Current treatment involves the use of antibiotics such as tetracycline (daily, for a period of 4 to 6 weeks) or azithromycin (single dose). Although effective in combating infection, re-infection generally occurs due to the endemic nature of the infection. Repeated infection over many years leads to scarring of the eyelid, distortion of the lid margin and rubbing of the eye lashes against the cornea (trichiasis). Constant trauma to the cornea is both painful and leads to corneal opacity and blindness (Mabey, D C W et al. The Lancet 2003 362:223-229).
Chlamydia pneumoniae is a major cause of acute respiratory tract infections in humans and is also believed to play a role in the pathogenesis of atherosclerosis and, in particular, coronary heart disease. Individuals with a high titer of antibodies to Chlamydia pneumoniae have been shown to be at least twice as likely to suffer from coronary heart disease as seronegative individuals.
Often chlamydial infection is asymptomatic and subclinical, such that severe and often irreversible complications may present as the first symptoms of genital infection. Infants born from a mother with a genital chlamydial infection may develop pneumonia and Chlamydia trachomatis is considered the most common causative agent of pneumonia during the first six months of life (de la Maza, L M et al. Curr. Opin. Investig. Drugs 2002 3(7):980-986).
Chlamydial infections thus constitute a significant health problem both in developed and developing countries. In light of the public health concerns, and the fact that the cost of current treatments is excessive in many developing countries, the development of vaccines for Chlamydia species has been an important research target. As the genomic make-up of Chlamydia trachomatis is relatively stable, and since the presence of animal reservoirs is negligible, even vaccines with limited efficacy may have a significant impact on the prevalence of infections.
There thus remains a need in the art for improved vaccines and pharmaceutical compositions for the prevention and treatment of Chlamydia infections. There also remains a need in the art for multivalent vaccines for the prevention and treatment of Chlamydia trachomatis infections which are effective against a range of serovars. The present invention fulfills these needs and further provides other related advantages.